1-(2,4-dichlorophenyl)-2-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)ethan-1-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2,4-dichlorophenyl)-2-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)ethan-1-one
• 英文别名: α-(3,5-dimethyl-1,2,4-triazol-1-yl)-2,4-dichloroacetophenone；1-(2,4-Dichlorophenyl)-2-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)ethanone；1-(2,4-dichlorophenyl)-2-(3,5-dimethyl-1,2,4-triazol-1-yl)ethanone
• 化学式: C₁₂H₁₁Cl₂N₃O
• mdl: MFCD00804956
• 分子量: 284.145
• InChiKey: VPKTVKSMTNWTIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  47.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2,4-dichlorophenyl)-2-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)ethan-1-one 在 三氟甲磺酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 64.0h， 生成 1-(sec-butyl)-4-(4-(4-(4-(((2S,4R)-2-(2,4-dichlorophenyl)-2-((3,5-dimethyl-1H-1,2,4-triazol-1-yl)methyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazin-1-yl)phenyl)-1H-1,2,4-triazol-5(4H)-one
  参考文献：
  名称：

  Novel Tetrazole-Containing Analogues of Itraconazole as Potent Antiangiogenic Agents with Reduced Cytochrome P450 3A4 Inhibition

  摘要：

  Itraconazole has been found to possess potent antiangiogenic activity, exhibiting promising antitumor activity in several human clinical studies. The wider use of itraconazole in the treatment of cancer, however, has been limited by its potent inhibition of the drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4). In an effort to eliminate the CYP3A4 inhibition while retaining its antiangiogenic activity, we designed and synthesized a series of derivatives in which the 1,2,4-triazole ring is replaced with various azoles and nonazoles. Among these analogues, 15n with tetrazole in place of 1,2,4-triazole exhibited optimal inhibition of human umbilical vein endothelial cell proliferation with an IC50 of 73 nM without a significant effect on CYP3A4 (EC50 > 20 mu M). Similar to itraconazole, 15n induced Niemann-Pick C phenotype (NPC phenotype) and blocked AMPK/mechanistic target of rapamycin signaling. These results suggest that 15n is a promising angiogenesis inhibitor that can be used in combination with most other known anticancer drugs.

  DOI：

  10.1021/acs.jmedchem.8b01252
• 作为产物：
  描述：

  1,3-二氯苯 在 aluminum (III) chloride 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 16.67h， 生成 1-(2,4-dichlorophenyl)-2-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)ethan-1-one
  参考文献：
  名称：

  Novel Tetrazole-Containing Analogues of Itraconazole as Potent Antiangiogenic Agents with Reduced Cytochrome P450 3A4 Inhibition

  摘要：

  Itraconazole has been found to possess potent antiangiogenic activity, exhibiting promising antitumor activity in several human clinical studies. The wider use of itraconazole in the treatment of cancer, however, has been limited by its potent inhibition of the drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4). In an effort to eliminate the CYP3A4 inhibition while retaining its antiangiogenic activity, we designed and synthesized a series of derivatives in which the 1,2,4-triazole ring is replaced with various azoles and nonazoles. Among these analogues, 15n with tetrazole in place of 1,2,4-triazole exhibited optimal inhibition of human umbilical vein endothelial cell proliferation with an IC50 of 73 nM without a significant effect on CYP3A4 (EC50 > 20 mu M). Similar to itraconazole, 15n induced Niemann-Pick C phenotype (NPC phenotype) and blocked AMPK/mechanistic target of rapamycin signaling. These results suggest that 15n is a promising angiogenesis inhibitor that can be used in combination with most other known anticancer drugs.

  DOI：

  10.1021/acs.jmedchem.8b01252

文献信息

• Rearrangement of enol acetates of ?-(3,5-dimethyl-1,2,4-triazol-1-yl)-2,4-dichloroacetophenone and ?-(1,2,4-triazol-1-yl)-2,4-dichloropropiophenone
  作者：O. M. Radul、M. Z. Krimer

  DOI：10.1007/bf00696985

  日期：1995.1

  At 140 degrees C in acetic anhydride enol acetates of alpha-(3,5-dimethyl-1,2,4-triazol-1-yl)-2,4-dichloroacetophenone and alpha-(1,2,4-triazol-1-yl)-2,4-dichloropropiophenone undergo 1,3- and 1,5-rearrangement, respectively.
• Novel Tetrazole-Containing Analogues of Itraconazole as Potent Antiangiogenic Agents with Reduced Cytochrome P450 3A4 Inhibition
  作者：Yingjun Li、Kalyan Kumar Pasunooti、Ruo-Jing Li、Wukun Liu、Sarah A. Head、Wei Q. Shi、Jun O. Liu

  DOI：10.1021/acs.jmedchem.8b01252

  日期：2018.12.27

  Itraconazole has been found to possess potent antiangiogenic activity, exhibiting promising antitumor activity in several human clinical studies. The wider use of itraconazole in the treatment of cancer, however, has been limited by its potent inhibition of the drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4). In an effort to eliminate the CYP3A4 inhibition while retaining its antiangiogenic activity, we designed and synthesized a series of derivatives in which the 1,2,4-triazole ring is replaced with various azoles and nonazoles. Among these analogues, 15n with tetrazole in place of 1,2,4-triazole exhibited optimal inhibition of human umbilical vein endothelial cell proliferation with an IC50 of 73 nM without a significant effect on CYP3A4 (EC50 > 20 mu M). Similar to itraconazole, 15n induced Niemann-Pick C phenotype (NPC phenotype) and blocked AMPK/mechanistic target of rapamycin signaling. These results suggest that 15n is a promising angiogenesis inhibitor that can be used in combination with most other known anticancer drugs.